Performance of the new biological small- and wide-angle X-ray scattering beamline 13A at the Taiwan Photon Source.

Recent developments in the instrumentation and data analysis of synchrotron small-angle X-ray scattering (SAXS) on biomolecules in solution have made biological SAXS (BioSAXS) a mature and popular tool in structural biology. This article reports on an advanced endstation developed at beamline 13A of the 3.0 GeV Taiwan Photon Source for biological small- and wide-angle X-ray scattering (SAXS-WAXS or SWAXS). The endstation features an in-vacuum SWAXS detection system comprising two mobile area detectors (Eiger X 9M/1M) and an online size-exclusion chromatography system incorporating several optical probes including a UV-Vis absorption spectrometer and refractometer. The instrumentation and automation allow simultaneous SAXS-WAXS data collection and data reduction for high-throughput biomolecular conformation and composition determinations. The performance of the endstation is illustrated with the SWAXS data collected for several model proteins in solution, covering a scattering vector magnitude q across three orders of magnitude. The crystal-model fittings to the data in the q range ∼0.005-2.0 Å-1 indicate high similarity of the solution structures of the proteins to their crystalline forms, except for some subtle hydration-dependent local details. These results open up new horizons of SWAXS in studying correlated local and global structures of biomolecules in solution.

New horizons in neurometabolic and neurovascular coupling from calibrated fMRI.

Neurovascular coupling relates changes in neuronal activity to constriction/dilation of microvessels. However neurometabolic coupling, which is less well known, relates alterations in neuronal activity with metabolic demands. The link between the blood oxygenation level dependent (BOLD) signal and neural activity opened doors for functional MRI (fMRI) to be a powerful neuroimaging tool in the neurosciences. But due to the complex makeup of BOLD contrast, researchers began to investigate the relationship between BOLD signal and blood flow and/or volume changes during functional brain activation, which together provided the tools to measure oxygen consumption on the basis of the biophysical model of BOLD. This field is called calibrated fMRI, thereby allowed probing of both neurometabolic and neurovascular couplings for a variety of health conditions in animals and humans. Calibrated fMRI may provide brain disorder biomarkers that could be used for monitoring effective therapies.

Adenovirus pulmonary infections identified by PCR and in situ hybridisation in bone marrow transplant recipients.

AIMS: To investigate adenovirus pulmonary infections in bone marrow transplant (BMT) recipients. METHODS: Formalin fixed, paraffin wax embedded lung tissue was examined from 13 necropsy cases after BMT using PCR and in situ hybridisation to detect adenovirus DNA. The E1A region of the adenoviral genome was targeted for PCR. In situ hybridisation was performed only in the PCR positive cases. RESULTS: Of the 13 lung specimens analysed, nine cases were negative for adenoviral nucleic acid. Four (30%) PCR and two (15%) in situ hybridisation positive cases were found. In some of the patients there were clinical and pathological indications that some diseases might be associated with adenovirus infection--haemorrhagic cystitis (three cases); necrotising pneumonia (one case). In necrotising pneumonia in which no pathogenic agents had been shown by conventional histological study, the in situ hybridisation technique showed positive staining for adenovirus. In a patient who died of renal failure caused by adenovirus nephritis, both PCR and in situ hybridisation were positive in the lung as well as in the kidney, although no histological change was found. Two PCR positive cases lacked positive sites for adenovirus by in situ hybridisation. CONCLUSIONS: The combination of PCR and in situ hybridisation could be useful for diagnosing adenovirus infection of the lung in BMT recipients. These results provide a basis for exploring further the clinical use of PCR and in situ hybridisation to diagnose adenovirus infection.

Switching transient analysis of a metal/ferroelectric/semiconductor switch diode with high speed response to infrared light.

A thin PbTiO(3)-n-p(+) silicon switch diode has been developed, in which the switching voltage (the turned-on voltage) changes in proportion to the infrared light power. The diode has a rapid response time of 0.65 mus compared with other conventional infrared sensors. It is attributed to the rapid switching device structure and the smaller pyroelectric layer thickness, 50 nm. In this paper, we have analyzed the rapid switching transient response by using heat conduction and switching theory successfully. The experimental results are in agreement with the theoretical analysis.

Selective cytotoxicity of azatyrosinamides against ras-transformed NIH 3T3 cells.

This study aims to develop novel azatyrosinamide compounds structurally modified from ras-specific antioncogenic azatyrosine. Analogues 4-15 were prepared and their inhibition on the growth of wild-type and ras-transformed NIH 3T3 cell lines was compared. Compound 12 was found to be the most active with IC50 16.5+/-2.2 microM which is 458-fold more potent than that of azatyrosine. The selective toxicity, defined as IC(50 wild-type)/IC(50 ras-transformed) for this compound was 138.5.

Influences of cisplatin combination chemotherapy on oxygen radical generation by blood in elderly and adult patients with lung cancer.

Oxygen radical generation by blood cells before and after chemotherapy was investigated in 16 elderly (72.8 +/- 1.0 years) and 14 adult (45.0 +/- 2.4 years) patients with lung cancer, using a lucigenin-dependent chemiluminescence method. The oxygen radical generation by 100 microliters of blood before chemotherapy in the elderly and the adults was 3,784 +/- 123 and 3,969 +/- 125 chemiluminescence (CL), respectively. The value decreased gradually and reached a nadir at 2 weeks after therapy (elderly: 1,090 +/- 37; adult: 1,114 +/- 38 CL). Peripheral leukocyte counts also reached a nadir then: 1,308 +/- 140 and 1,288 +/- 44/mm3, respectively. However, the oxygen-radical-generating activity per leukocyte was not different before and after the therapy (elderly: 0.94 +/- 0.14 CL before to 0.83 +/- 0.09 CL after; adult: 0.97 +/- 0.13 CL before to 0.87 +/- 0.10 CL after). These results indicate that a decrease in oxygen radical generation by blood following chemotherapy is mainly due to a decrease in the number of polymorphonuclear neutrophils both in elderly and adult patients.

Increased spontaneous production and generation of superoxide anion by blood neutrophils in patients with asthma.

Spontaneous production and PMA- and opsonized zymosan- stimulated generation of superoxide anion by blood cells in asthmatic patients were compared with those in normal volunteers and chronic obstructive pulmonary disease (COPD) patients using a lucigenin-dependent chemiluminescence method. Superoxide anion generation by 100 microl of blood in patients with asthma and/or COPD was significantly greater than that in normal subjects [asthma: 5684 +/- 253 chemiluminescence (CL); COPD: 4994 +/- 240 CL; normal: 2543 +/- 213CL]. This is consistent with the increased superoxide generation per leukocyte (PMN) in these patients (Asthma: 1.56 +/- 0.08 CL/PMN; COPD: 1.31 +/- 0.08 CL/PMN; normal: 0.83 +/- 0.07 CL/PMN. However, spontaneous production of superoxide by individual PMNs was increased only in asthmatic patients, compared with that in normal subjects (Asthma: 0.14 +/- 0.02 CL/PMN; COPD: 0.07 +/- 0.01 CL/PMN; normal: 0.07 +/- 0.01 CL/PMN. These results indicate that the respiratory burst is enhanced in both asthmatic patients and COPD patients, and that superoxide production by resting neutrophils is also increased in asthmatic patients, but not in COPD patients, compared with normal subjects.

Superoxide anion formation and glutathione metabolism of blood in patients with idiopathic pulmonary fibrosis.

The oxidant-antioxidant imbalance in the lower respiratory tract plays a major role in the pathogenesis in idiopathic pulmonary fibrosis (IPF). However, the systemic oxidant-antioxidant balance in the patients with IPF has not been extensively evaluated. In this study, the metabolism of glutathione (GSH) and superoxide anion production of whole blood were tested in 14 IPF patients and 12 normal subjects. While the total amount of GSH in the blood of IPF patients was not different from that of normal subjects (IPF; 22.9 +/- 4.9 micrograms/ml, control; 26.1 +/- 3.7 micrograms/ml), the amount of oxidized GSH (GSSG) and the ratio of GSSG to the total GSH in blood significantly increased in patients with IPF (IPF; 14.4 +/- 3.5%, control; 7.0 +/- 1.7%, P < 0.01), indicating that the glutathione redox cycle may be impaired in IPF. The production and generation of superoxide anions by blood were significantly greater in IPF than in normal subjects. The level of superoxide anion production was correlated with the GSSG/GSH ratio. These results indicate that IPF patients exhibit an impaired GSH metabolism with an increased oxidant formation of blood.